Acetic Acid → 1,3-Dihydro-5-nitro-1′-[[2-(trimethylsilyl)ethoxy]methyl]spiro[2H-indene-2,3′-[3H]pyrrolo[2,3-b]pyridin]-2′(1′H)-one

HRID 1675741Notes

Reaction equation

HRID 1675741 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[CH2:12]Br.[CH3:14][Si:15]([CH3:31])([CH3:30])[CH2:16][CH2:17][O:18][CH2:19][N:20]1[C:24]2=[N:25][CH:26]=[CH:27][CH:28]=[C:23]2[CH2:22][C:21]1=[O:29].C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(=O)C>CN(C=O)C>[N+:9]([C:6]1[CH:5]=[C:4]2[C:3](=[CH:8][CH:7]=1)[CH2:2][C:22]1([C:23]3[C:24](=[N:25][CH:26]=[CH:27][CH:28]=3)[N:20]([CH2:19][O:18][CH2:17][CH2:16][Si:15]([CH3:30])([CH3:14])[CH3:31])[C:21]1=[O:29])[CH2:12]2)([O-:11])=[O:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 10796Cesium carbonateHCID 108523601,2-Bis(bromomethyl)-4-nitrobenzeneHCID 574588861-{[2-(Trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one

Product 1

HCID 591667381,3-Dihydro-5-nitro-1′-[[2-(trimethylsilyl)ethoxy]methyl]spiro[2H-indene-2,3′-[3H]pyrrolo[2,3-b]pyridin]-2′(1′H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1,2-bis(bromomethyl)-4-nitrobenzene from Step E (40.9 g, 132 mmol) and 1-{[2-(trimethylsilyl)ethoxy]methyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one from Step C (31.5 g, 119 mmol) in DMF (2 L) was added cesium carbonate (129 g, 397 mmol) portion wise, over 5 min. After 18 h, acetic acid (7.6 mL) was added and the mixture was concentrated to a volume of about 500 mL, then partitioned between EtOAc (1.5 L) and H2O (1 L). The organic layer was washed with H2O (1 L), then brine (500 mL), then dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc-100:0 to 0:100, to give the title compound. MS: m/z=412 (M+1).

Workup

  1. waitAfter 18 h
  2. concentrationthe mixture was concentrated to a volume of about 500 mL
  3. custompartitioned between EtOAc (1.5 L) and H2O (1 L)
  4. washThe organic layer was washed with H2O (1 L)
  5. dry with materialbrine (500 mL), then dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-19e178cf30bf49f9be48f1eb427a3e85
Source dataset
uspto-grants-2011_08
Patent number
US08003792B2

Reaction notes

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